APL Bioengineering最新文献

{"title":"Revolutionizing biomedical research: The imperative need for heart-kidney-connected organoids.","authors":"Sun-Sook Song, Hun-Jun Park, Yong Kyun Kim, Sun-Woong Kang","doi":"10.1063/5.0190840","DOIUrl":"10.1063/5.0190840","url":null,"abstract":"<p><p>Organoids significantly advanced our comprehension of organ development, function, and disease modeling. This Perspective underscores the potential of heart-kidney-connected organoids in understanding the intricate relationship between these vital organs, notably the cardiorenal syndrome, where dysfunction in one organ can negatively impact the other. Conventional models fall short in replicating this complexity, necessitating an integrated approach. By co-culturing heart and kidney organoids, combined with microfluidic and 3D bioprinting technologies, a more accurate representation of <i>in vivo</i> conditions can be achieved. Such interconnected systems could revolutionize our grasp of multi-organ diseases, drive drug discovery by evaluating therapeutic agents on both organs simultaneously, and reduce the need for animal models. In essence, heart-kidney-connected organoids present a promising avenue to delve deeper into the pathophysiology underlying cardiorenal disorders, bridging existing knowledge gaps, and advancing biomedical research.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"010902"},"PeriodicalIF":6.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10901547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D convolutional neural networks predict cellular metabolic pathway use from fluorescence lifetime decay data.","authors":"Linghao Hu, Daniela De Hoyos, Yuanjiu Lei, A Phillip West, Alex J Walsh","doi":"10.1063/5.0188476","DOIUrl":"10.1063/5.0188476","url":null,"abstract":"<p><p>Fluorescence lifetime imaging of the co-enzyme reduced nicotinamide adenine dinucleotide (NADH) offers a label-free approach for detecting cellular metabolic perturbations. However, the relationships between variations in NADH lifetime and metabolic pathway changes are complex, preventing robust interpretation of NADH lifetime data relative to metabolic phenotypes. Here, a three-dimensional convolutional neural network (3D CNN) trained at the cell level with 3D NAD(P)H lifetime decay images (two spatial dimensions and one time dimension) was developed to identify metabolic pathway usage by cancer cells. NADH fluorescence lifetime images of MCF7 breast cancer cells with three isolated metabolic pathways, glycolysis, oxidative phosphorylation, and glutaminolysis were obtained by a multiphoton fluorescence lifetime microscope and then segmented into individual cells as the input data for the classification models. The 3D CNN models achieved over 90% accuracy in identifying cancer cells reliant on glycolysis, oxidative phosphorylation, or glutaminolysis. Furthermore, the model trained with human breast cancer cell data successfully predicted the differences in metabolic phenotypes of macrophages from control and POLG-mutated mice. These results suggest that the integration of autofluorescence lifetime imaging with 3D CNNs enables intracellular spatial patterns of NADH intensity and temporal dynamics of the lifetime decay to discriminate multiple metabolic phenotypes. Furthermore, the use of 3D CNNs to identify metabolic phenotypes from NADH fluorescence lifetime decay images eliminates the need for time- and expertise-demanding exponential decay fitting procedures. In summary, metabolic-prediction CNNs will enable live-cell and <i>in vivo</i> metabolic measurements with single-cell resolution, filling a current gap in metabolic measurement technologies.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016112"},"PeriodicalIF":6.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10901549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-scale numerical approach to study monoclonal antibodies in solution.","authors":"Marco Polimeni, Emanuela Zaccarelli, Alessandro Gulotta, Mikael Lund, Anna Stradner, Peter Schurtenberger","doi":"10.1063/5.0186642","DOIUrl":"10.1063/5.0186642","url":null,"abstract":"<p><p>Developing efficient and robust computational models is essential to improve our understanding of protein solution behavior. This becomes particularly important to tackle the high-concentration regime. In this context, the main challenge is to put forward coarse-grained descriptions able to reduce the level of detail, while retaining key features and relevant information. In this work, we develop an efficient strategy that can be used to investigate and gain insight into monoclonal antibody solutions under different conditions. We use a multi-scale numerical approach, which connects information obtained at all-atom and amino-acid levels to bead models. The latter has the advantage of reproducing the properties of interest while being computationally much faster. Indeed, these models allow us to perform many-protein simulations with a large number of molecules. We can, thus, explore conditions not easily accessible with more detailed descriptions, perform effective comparisons with experimental data up to very high protein concentrations, and efficiently investigate protein-protein interactions and their role in phase behavior and protein self-assembly. Here, a particular emphasis is given to the effects of charges at different ionic strengths.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016111"},"PeriodicalIF":6.6,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluid shear stress induced-endothelial phenotypic transition contributes to cerebral ischemia-reperfusion injury and repair.","authors":"Denglian Sun, Jia Ma, Lingyu Du, Qiao Liu, Hongyan Yue, Chengxiu Peng, Hanxiao Chen, Guixue Wang, Xiaoheng Liu, Yang Shen","doi":"10.1063/5.0174825","DOIUrl":"10.1063/5.0174825","url":null,"abstract":"<p><p>Long-term ischemia leads to insufficient cerebral microvascular perfusion and dysfunction. Reperfusion restores physiological fluid shear stress (FSS) but leads to serious injury. The mechanism underlying FSS-induced endothelial injury in ischemia-reperfusion injury (IRI) remains poorly understood. In this study, a rat model of middle cerebral artery occlusion was constructed to explore cerebrovascular endothelial function and inflammation <i>in vivo</i>. Additionally, the rat brain microvascular endothelial cells (rBMECs) were exposed to a laminar FSS of 0.5 dyn/cm² for 6 h and subsequently restored to physiological fluid shear stress level (2 dyn/cm²) for 2 and 12 h, respectively. We found that reperfusion induced endothelial-to-mesenchymal transition (EndMT) in endothelial cells, leading to serious blood-brain barrier dysfunction and endothelial inflammation, accompanied by the nuclear accumulation of Yes-associated protein (YAP). During the later stage of reperfusion, cerebral endothelium was restored to the endothelial phenotype with a distinct change in mesenchymal-to-endothelial transition (MEndT), while YAP was translocated and phosphorylated in the cytoplasm. Knockdown of YAP or inhibition of actin polymerization markedly impaired the EndMT in rBMECs. These findings suggest that ischemia-reperfusion increased intensity of FSS triggered an EndMT process and, thus, led to endothelial inflammation and tissue injury, whereas continuous FSS induced a time-dependent reversal MEndT event contributing to the endothelial repair. This study provides valuable insight for therapeutic strategies targeting IRI.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016110"},"PeriodicalIF":6.0,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10898918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement of clinical wound microcirculation diagnosis using an object tracking-based laser speckle contrast imaging system.","authors":"Meng-Che Hsieh, Chia-Yu Chang, Ching-Han Hsu, Yan-Ren Lin, Pei-You Hsieh, Congo Tak-Shing Ching, Lun-De Liao","doi":"10.1063/5.0172443","DOIUrl":"10.1063/5.0172443","url":null,"abstract":"<p><p>Wound monitoring is crucial for effective healing, as nonhealing wounds can lead to tissue ulceration and necrosis. Evaluating wound recovery involves observing changes in angiogenesis. Laser speckle contrast imaging (LSCI) is vital for wound assessment due to its rapid imaging, high resolution, wide coverage, and noncontact properties. When using LSCI equipment, regions of interest (ROIs) must be delineated in lesion areas in images for quantitative analysis. However, patients with serious wounds cannot maintain constant postures because the affected areas are often associated with discomfort and pain. This leads to deviations between the drawn ROI and actual wound position when using LSCI for wound assessment, affecting the reliability of relevant assessments. To address these issues, we used the channel and spatial reliability tracker object tracking algorithm to develop an automatic ROI tracking function for LSCI systems. This algorithm is used to track and correct artificial movements in blood flow images, address the ROI position offset caused by the movement of the affected body part, increase the blood flow analysis accuracy, and improve the clinical applicability of LSCI systems. ROI tracking experiments were performed by simulating wounds, and the results showed that the intraclass correlation coefficient (ICC) ranged from 0.134 to 0.976. Furthermore, the object within the ROI affected tracking performance. Clinical assessments across wound types showed ICCs ranging from 0.798 to 0.917 for acute wounds and 0.628-0.849 for chronic wounds. We also discuss factors affecting tracking performance and propose strategies to enhance implementation effectiveness.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016105"},"PeriodicalIF":6.6,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10827336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual delivery gene-activated scaffold directs fibroblast activity and keratinocyte epithelization.","authors":"Ashang L Laiva, Fergal J O'Brien, Michael B Keogh","doi":"10.1063/5.0174122","DOIUrl":"10.1063/5.0174122","url":null,"abstract":"<p><p>Fibroblasts are the most abundant cell type in dermal skin and keratinocytes are the most abundant cell type in the epidermis; both play a crucial role in wound remodeling and maturation. We aim to assess the functionality of a novel dual gene activated scaffold (GAS) on human adult dermal fibroblasts (hDFs) and see how the secretome produced could affect human dermal microvascular endothelial cells (HDMVECs) and human epidermal keratinocyte (hEKs) growth and epithelization. Our GAS is a collagen chondroitin sulfate scaffold loaded with pro-angiogenic stromal derived factor (SDF-1α) and/or an anti-aging β-Klotho plasmids. hDFs were grown on GAS for two weeks and compared to gene-free scaffolds. GAS produced a significantly better healing outcome in the fibroblasts than in the gene-free scaffold group. Among the GAS groups, the dual GAS induced the most potent pro-regenerative maturation in fibroblasts with a downregulation in proliferation (twofold, p < 0.05), fibrotic remodeling regulators TGF-β1 (1.43-fold, p < 0.01) and CTGF (1.4-fold, p < 0.05), fibrotic cellular protein α-SMA (twofold, p < 0.05), and fibronectin matrix deposition (twofold, p < 0.05). The dual GAS secretome also showed enhancements of paracrine keratinocyte pro-epithelializing ability (1.3-fold, p < 0.05); basement membrane regeneration through laminin (6.4-fold, p < 0.005) and collagen IV (8.7-fold, p < 0.005) deposition. Our findings demonstrate enhanced responses in dual GAS containing hDFs by proangiogenic SDF-1α and β-Klotho anti-fibrotic rejuvenating activities. This was demonstrated by activating hDFs on dual GAS to become anti-fibrotic in nature while eliciting wound repair basement membrane proteins; enhancing a proangiogenic HDMVECs paracrine signaling and greater epithelisation of hEKs.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016104"},"PeriodicalIF":6.6,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10821797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A fully automated deep learning approach for coronary artery segmentation and comprehensive characterization.","authors":"Guido Nannini, Simone Saitta, Andrea Baggiano, Riccardo Maragna, Saima Mushtaq, Gianluca Pontone, Alberto Redaelli","doi":"10.1063/5.0181281","DOIUrl":"10.1063/5.0181281","url":null,"abstract":"<p><p>Coronary computed tomography angiography (CCTA) allows detailed assessment of early markers associated with coronary artery disease (CAD), such as coronary artery calcium (CAC) and tortuosity (CorT). However, their analysis can be time-demanding and biased. We present a fully automated pipeline that performs (i) coronary artery segmentation and (ii) CAC and CorT objective analysis. Our method exploits supervised learning for the segmentation of the lumen, and then, CAC and CorT are automatically quantified. 281 manually annotated CCTA images were used to train a two-stage U-Net-based architecture. The first stage employed a 2.5D U-Net trained on axial, coronal, and sagittal slices for preliminary segmentation, while the second stage utilized a multichannel 3D U-Net for refinement. Then, a geometric post-processing was implemented: vessel centerlines were extracted, and tortuosity score was quantified as the count of branches with three or more bends with change in direction forming an angle >45°. CAC scoring relied on image attenuation. CAC was detected by setting a patient specific threshold, then a region growing algorithm was applied for refinement. The application of the complete pipeline required <5 min per patient. The model trained for coronary segmentation yielded a Dice score of 0.896 and a mean surface distance of 1.027 mm compared to the reference ground truth. Tracts that presented stenosis were correctly segmented. The vessel tortuosity significantly increased locally, moving from proximal, to distal regions (p < 0.001). Calcium volume score exhibited an opposite trend (p < 0.001), with larger plaques in the proximal regions. Volume score was lower in patients with a higher tortuosity score (p < 0.001). Our results suggest a linked negative correlation between tortuosity and calcific plaque formation. We implemented a fast and objective tool, suitable for population studies, that can help clinician in the quantification of CAC and various coronary morphological parameters, which is helpful for CAD risk assessment.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016103"},"PeriodicalIF":6.6,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo label-free tissue histology through a microstructured imaging window","authors":"C. Conci, L. Sironi, E. Jacchetti, D. Panzeri, D. Inverso, R. Martínez Vázquez, R. Osellame, M. Collini, G. Cerullo, Giuseppe Chirico, M. Raimondi","doi":"10.1063/5.0165411","DOIUrl":"https://doi.org/10.1063/5.0165411","url":null,"abstract":"Tissue histopathology, based on hematoxylin and eosin (H&E) staining of thin tissue slices, is the gold standard for the evaluation of the immune reaction to the implant of a biomaterial. It is based on lengthy and costly procedures that do not allow longitudinal studies. The use of non-linear excitation microscopy in vivo, largely label-free, has the potential to overcome these limitations. With this purpose, we develop and validate an implantable microstructured device for the non-linear excitation microscopy assessment of the immune reaction to an implanted biomaterial label-free. The microstructured device, shaped as a matrix of regular 3D lattices, is obtained by two-photon laser polymerization. It is subsequently implanted in the chorioallantoic membrane (CAM) of embryonated chicken eggs for 7 days to act as an intrinsic 3D reference frame for cell counting and identification. The histological analysis based on H&E images of the tissue sections sampled around the implanted microstructures is compared to non-linear excitation and confocal images to build a cell atlas that correlates the histological observations to the label-free images. In this way, we can quantify the number of cells recruited in the tissue reconstituted in the microstructures and identify granulocytes on label-free images within and outside the microstructures. Collagen and microvessels are also identified by means of second-harmonic generation and autofluorescence imaging. The analysis indicates that the tissue reaction to implanted microstructures is like the one typical of CAM healing after injury, without a massive foreign body reaction. This opens the path to the use of similar microstructures coupled to a biomaterial, to image in vivo the regenerating interface between a tissue and a biomaterial with label-free non-linear excitation microscopy. This promises to be a transformative approach, alternative to conventional histopathology, for the bioengineering and the validation of biomaterials in in vivo longitudinal studies.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"57 15","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139441997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the reliability of the evoked response in human iPSCs-derived neuronal networks coupled to micro-electrode arrays.","authors":"Giorgia Zanini, Giulia Parodi, Michela Chiappalone, Sergio Martinoia","doi":"10.1063/5.0174227","DOIUrl":"10.1063/5.0174227","url":null,"abstract":"<p><p><i>In vitro</i> models of neuronal networks have emerged as a potent instrument for gaining deeper insights into the intricate mechanisms governing the human brain. Notably, the integration of human-induced pluripotent stem cells (hiPSCs) with micro-electrode arrays offers a means to replicate and dissect both the structural and functional elements of the human brain within a controlled <i>in vitro</i> environment. Given that neuronal communication relies on the emission of electrical (and chemical) stimuli, the employment of electrical stimulation stands as a mean to comprehensively interrogate neuronal assemblies, to better understand their inherent electrophysiological dynamics. However, the establishment of standardized stimulation protocols for cultures derived from hiPSCs is still lacking, thereby hindering the precise delineation of efficacious parameters to elicit responses. To fill this gap, the primary objective of this study resides in delineating effective parameters for the electrical stimulation of hiPSCs-derived neuronal networks, encompassing the determination of voltage amplitude and stimulation frequency able to evoke reliable and stable responses. This study represents a stepping-stone in the exploration of efficacious stimulation parameters, thus broadening the electrophysiological activity profiling of neural networks sourced from human-induced pluripotent stem cells.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 4","pages":"046121"},"PeriodicalIF":6.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10735322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138832212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered blood flow due to larger aortic diameters in patients with transcatheter heart valve thrombosis.","authors":"Silje Ekroll Jahren, Caglayan Demirel, Karoline-Marie Bornemann, Pascal Corso, Stefan Stortecky, Dominik Obrist","doi":"10.1063/5.0170583","DOIUrl":"https://doi.org/10.1063/5.0170583","url":null,"abstract":"<p><p>The etiology of transcatheter heart valve thrombosis (THVT) and the relevance of the aortic root geometry on the occurrence of THVT are largely unknown. The first aim of this pilot study is to identify differences in aortic root geometry between THVT patients and patients without THVT after transcatheter aortic valve implantation (TAVI). Second, we aim to investigate how the observed difference in aortic diameters affects the aortic flow using idealized computational geometric models. Aortic dimension was assessed using pre-TAVI multi-detector computed tomography scans of eight patients with clinical apparent THVT and 16 unaffected patients (two for each THVT patient with same valve type and size) from the Bern-TAVI registry. Among patients with THVT the right coronary artery height was lower (-40%), and sinotubular junction (STJ) and ascending aorta (AAo) diameters tended to be larger (9% and 14%, respectively) compared to the unaffected patients. Fluid-structure interaction (FSI) in two idealized aortic models with the observed differences in STJ and AAo diameter showed higher backflow rate at the STJ (+16%), lower velocity magnitudes in the sinus (-5%), and higher systolic turbulent dissipation rate in the AAo (+8%) in the model with larger STJ and AAo diameters. This pilot study suggests a direct effect of the aortic dimensions on clinically apparent THVT. The FSI study indicates that larger STJ and AAo diameters potentially favor thrombus formation by increased backflow rate and reduced wash-out efficiency of the sinus. The reported observations require clinical validation but could potentially help identifying patients at risk for THVT.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 4","pages":"046120"},"PeriodicalIF":6.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10732696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138832211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}